Nonisothermal stability assessment of stable pharmaceuticals: testing of a clindamycin phosphate formulation.

The stability of an antibiotic formulation (clindamycin phosphate in dextrose), which is stable at room temperature, was assessed by nonisothermal kinetic analysis at elevated temperatures. A preliminary study, conducted to establish apparent rate order, verified the appropriateness of a first-order kinetic model. The test formulation was then heated linearly from 70 to 90 degrees C over 12 hr. Data (drug concentration, temperature, and time) were fitted to the first-order model using nonlinear least-squares regression. Arrhenius parameter estimates obtained from three nonisothermal trials, and rate constants at 25 degrees C derived by extrapolation, demonstrated acceptable reproducibility and were in agreement with values derived from isothermal experiments at 30, 45, 55, 65, and 75 degrees C. First-order rate constants obtained from studies conducted for 20 months at 25 degrees C were in accord with isothermal and nonisothermal results.